Nucleic acid nanorobot assay for accurate and simplified ASO quantification in mouse plasma.

Authors

Åsa Sandelius, Cheryl Arrowsmith, Neil Henderson, Alexander W Jackson

Published in

Bioanalysis. Pages 1-9. Dec 09, 2025. Epub Dec 09, 2025.

Abstract

Pharmacokinetic (PK) characterization and accurate quantification is critical for drug development. The broad potential for antisense oligonucleotide (ASO) drugs to target previously undruggable pathways has resulted in a growing number of ASO therapeutics in development increasing the demand on bioanalysis for PK and safety characterization.
In this study, a nucleic acid nanorobot (NAN) assay based on toehold mediated strand displacement was for the first time developed for ASO bioanalysis in plasma using a timesaving and simplified 2-step procedure without need for nucleotide extraction. The assay was qualified in two different laboratories to determine precision, accuracy, dilutional linearity, and matrix interferences.
With the ASO driving a programmable cascade of RNA-DNA interaction resulting in release of a fluorophore, the NAN assay generates fluorescent signal proportional to analyte concentration. The assay showed high accuracy and precision across the assay range and high sensitivity. The assay was successfully transferred to a 2^nd laboratory, utilizing different equipment and software, providing evidence of assay robustness and accuracy in mouse plasma.
A NAN assay for ASO PK bioanalysis was for the first time assessed for performance and agreement between laboratories, demonstrating this as a viable additional alternative to current bioanalytical methodologies.

PMID:
41368817
Bibliographic data and abstract were imported from PubMed on 10 Dec 2025.

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